Vitamin D supplementation and prevention of cardiovascular disease and cancer in the Finnish Vitamin D Trial: a randomized controlled trial

Abstract

Background Vitamin D insufficiency is associated with risk of cardiovascular diseases (CVD) and cancer in observational studies, but evidence for benefits with vitamin D supplementation is limited. Objectives To investigate the effects of vitamin D3 supplementation on CVD and cancer incidence. Design The study was a 5-year randomized placebo-controlled trial among 2495 male participants ≥ 60 years and post-menopausal female participants ≥ 65 years from a general Finnish population who were free of prior CVD or cancer. The study had three arms: placebo, 1600 IU/day or 3200 IU/day vitamin D3. Follow-up was by annual study questionnaires and national registry data. A representative sub-cohort of 551 participants had more detailed in-person investigations. The primary endpoints were incident major CVD and invasive cancer. Secondary endpoints included the individual components of the primary CVD endpoint (myocardial infarction, stroke, and CVD mortality), site-specific cancers and cancer death. Results During the follow-up, there were 41 (4.9%), 42 (5.0%) and 36 (4.3%) major CVD events in the placebo, 1600 IU/d (vs. placebo: hazard ratio (HR), 0.97;95% CI, 0.63,1.49; P = 0.89), and 3200 IU/d (HR, 0.84;95% CI, 0.54,1.31; P = 0.44) arms, respectively. Invasive cancer was diagnosed in 41 (4.9%), 48 (5.8%) and 40 (4.8%) participants in the placebo, 1600 IU/d (HR, 1.14;95% CI, 0.75,1.72; P = 0.55), and 3200 IU/d (HR, 0.95;95% CI, 0.61,1.47; P = 0.81) arms, respectively. There were no significant differences in the secondary endpoints or total mortality. In the sub-cohort, the mean (standard deviation) baseline serum 25-hydroxyvitamin D concentration was 75 (18) nmol/L. After 12 months, the concentrations were 73 (18) nmol/L, 100 (21) nmol/L and 120 (22) nmol/L in the placebo, 1600 IU/d and 3200 IU/d arms, respectively. Conclusions Vitamin D3 supplementation did not lower the incidence of major CVD events or invasive cancer among older adults, possibly due to sufficient vitamin D status in most participants at baseline. Clinical Trial Registry number: ClinicalTrials.gov: NCT01463813, https://clinicaltrials.gov/ct2/show/NCT01463813.

Combined Vitamin D, Omega-3 Fatty Acids, and a Simple Home Exercise Program May Reduce Cancer Risk Among Active Adults Aged 70 and Older: A Randomized Clinical Trial

“…Furthermore, adherence to the interventions was high, with on average above 80% for the study medication and on average over 60% for performing the exercise program at least twice a week ( Bischoff-Ferrari et al, 2020 ). Furthermore, the rate of any new invasive cancer in DO-HEALTH participants aged 70 and older was representative for the age-group investigated ( White et al, 2014 ), between 3.8% (81 verified cases) and 5.2% (113 reported cases), compared with 1.2% in VITAL participants aged 50 years and older and a little less compared to the Finnish Vitamin D Trial with 5.2% (129 recorded cases) in participants aged ≥60 years ( Virtanen et al, 2022 ). Finally, the consistency of findings between the primary analysis and sensitivity analyses lends strength to our findings.…”

“…For vitamin D and cancer prevention, our trial tested a daily dose of 2000 IU vitamin D 3 , which according to a recent meta-analysis on cancer prevention, may have reduced cancer death on its own ( Keum et al, 2019 ), while an effect of Vitamin D on cancer incidence was not seen, neither in the 5-year Finnish Vitamin D Trial, where 1600 IU/d and 3200 IU/d were tested against placebo in 2,495 participants ≥60 years ( Virtanen et al, 2022 ), and the meta-analysis by Keum et al This meta-analysis evaluated ten RCTs (6,537 cases) and included the large VITAL trial ( Manson et al, 2019b ). Four of the included trials provided a large intermittent bolus of vitamin D 3 (20,000 IU/week–500,000 IU/year), and six trials provided vitamin D 3 in a daily dose (400–2000 IU/day) ( Keum et al, 2019 ).…”

Association between Vitamin D Supplementation and Cancer Mortality: A Systematic Review and Meta-Analysis

“…A total of 11 RCTs with a total of 51,369 participants were included in the meta-analysis for cancer incidence [ 14 , 30 , 32 , 34 , 35 , 37 , 38 , 41 , 42 , 43 , 45 , 46 ]. No significant association of vitamin D supplementation with overall cancer incidence was found (RR 0.99, 95% CI 0.93–1.06, I 2 = 0%; Figure 4 A).…”

Hypovitaminosis D and cardiovascular outcomes: A systematic review and meta-analysis

“…While this would support population-wide vitamin D supplementation to eradicate vitamin D deficiency, results from recent large randomized controlled trials (RCTs) are not supportive. VITAL trial, ViDA study and FIND trial found supplemental vitamin D not to be beneficial to reduce major cardiovascular events [26] , [27] , [28] . This was most probably due to an inadequate number of participants with very low vitamin D levels which would not permit detection of beneficial effects for relatively rare disease endpoints such as cardiovascular events.…”